The regulation of microtubule (MT) dynamics is crucial to many cellular processes. Post-translational tubulin modifications such as tubulin glutamylation are instrumental in regulating microtubule function; and influence cellular processes such as centriole stability, and neuronal and cilia functions. The recent demonstration that the tubulin tyrosine ligase like (TTLL) proteins are responsible for tubulin glutamylation opens the opportunity for the first in vivo analysis of the role of glutamylation. We are studying the function of glutamylation in cell division and development by analysis of mutant/RNAi phenotypes after disruption of the glutamylases in C. elegans. Our analysis of the distribution of glutamylated tubulin and tissue-specific expression of glutamylases will aid this study. Genome-wide screens have already described an embryonic lethal phenotype after RNAi of one TTLL, TTLL-5, and we are now investigating the basis for this phenotype. This should allow us to deduce the role of glutamylation in the embryo. Using reverse genetics we are attempting to identify mutations in TTLL-5 and other members of the TTLL family, which will facilitate the study of the roles of glutamylation in all stages of development.